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Onasemnogene Abeparvovec-Brve

FDA Drug Information • Also known as: Itvisma

Brand Names
Itvisma
Route
INTRATHECAL
Dosage Form
INJECTION, SUSPENSION
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: SERIOUS LIVER INJURY Acute serious liver injury and elevated aminotransferases can occur with ITVISMA. [see Warnings and Precautions (5.1)] Patients with preexisting liver impairment may be at higher risk. [see Warnings and Precautions (5.1)] Prior to intrathecal injection, assess liver function by clinical examination and laboratory testing. Administer systemic corticosteroid before and after ITVISMA injection. Continue to monitor liver function for at least 3 months after injection, and at other times as clinically indicated. [see Dosage and Administration (2.1, 2.4)]. WARNING: SERIOUS LIVER INJURY See full prescribing information for complete boxed warning. Acute serious liver injury and elevated aminotransferases can occur with ITVISMA. ( 5.1 ) Patients with preexisting liver impairment may be at higher risk. ( 5.1 ) Prior to intrathecal injection, assess liver function by clinical examination and laboratory testing. Administer systemic corticosteroid before and after ITVISMA injection. Continue to monitor liver function for at least 3 months after injection, and at other times as clinically indicated. ( 2.1 , 2.4 )

Description

11 DESCRIPTION ITVISMA (onasemnogene abeparvovec-brve) is a suspension of an adeno-associated viral vector-based gene therapy for intrathecal injection. It is a recombinant self-complementary AAV9 containing a transgene encoding the human survival motor neuron (SMN) protein, under the control of a cytomegalovirus enhancer/chickenβactin hybrid promoter. ITVISMA has a nominal concentration of 4 × 10 13 vg/mL. Each vial contains an extractable volume of not less than 3 mL and the excipients 20 mM Tris (pH 8.0), 1 mM magnesium chloride (MgCl 2 ), 200 mM sodium chloride (NaCl) and 0.005% poloxamer 188. ITVISMA is packaged as a sterile suspension and contains no preservative.

What Is Onasemnogene Abeparvovec-Brve Used For?

1 INDICATIONS AND USAGE ITVISMA is indicated for the treatment of spinal muscular atrophy (SMA) in adult and pediatric patients 2 years of age and older with confirmed mutation in survival motor neuron 1 (SMN1) gene. ITVISMA is an adeno-associated virus (AAV) vector-based gene therapy indicated for the treatment of spinal muscular atrophy (SMA) in adult and pediatric patients 2 years of age and older with confirmed mutation in SMN1 gene. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For single-dose intrathecal injection only. ( 2 ) The recommended dose of ITVISMA is 1.2 × 10 14 vector genomes (vg). ( 2.2 ) Administer ITVISMA as an intrathecal bolus injection over approximately 1 to 2 minutes. ( 2.4 ) Postpone ITVISMA in patients with infections until the infection has resolved and the patient is clinically stable. ( 2.1 ) Starting one day prior to ITVISMA injection, administer systemic corticosteroids equivalent to oral prednisolone at 1 mg/kg of body weight per day for a total of 30 days. At the end of the 30-day period, check liver function by clinical examination and by laboratory testing. For patients with unremarkable findings, taper the corticosteroid dose gradually over the next 28 days. If liver function abnormalities persist, continue systemic corticosteroids (equivalent to oral prednisolone at 1 mg/kg/day) until findings become unremarkable, and then taper the corticosteroid dose gradually over the next 28 days or longer if needed. Do not stop systemic corticosteroids abruptly. ( 2.2 ) If at any time patients do not respond adequately to the equivalent of 1 mg/kg/day oral prednisolone, based on the patient’s clinical course, prompt consultation with a gastroenterologist or hepatologist and adjustment to the recommended corticosteroid regimen may be considered. ( 2.2 ) 2.1 Critical Dosing Information For single-dose intrathecal injection only. Patients previously treated with ZOLGENSMA (onasemnogene abeparvovec-xioi) should not be treated with ITVISMA [see Clinical Pharmacology (12.1)] . ITVISMA should only be administered intrathecally using a lumbar puncture by healthcare professionals (e.g., interventional radiologist or neurologist) experienced in performing lumbar punctures. Prior to ITVISMA injection: Due to the increased risk of serious systemic immune response, administer ITVISMA to patients who are clinically stable in their overall baseline health status (e.g., hydration and nutritional status, absence of infection, respiratory status) prior to administration. Postpone ITVISMA in patients with active or recent infections, until the infection has resolved, and the patient is clinically stable. Clinical signs or symptoms of infection should not be evident at the time of ITVISMA injection. Assess vaccination status. Vaccination status should be up-to-date prior to ITVISMA administration. Recommend seasonal prophylaxis against respiratory syncytial virus (RSV). Assess liver function (clinical examination and laboratory testing including aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, prothrombin time, partial thromboplastin time (PTT), international normalized ratio (INR), and total bilirubin) [see Warnings and Precautions (5.1), Use in Specific Populations (8.6)] . Obtain creatinine and complete blood count (including hemoglobin and platelet count) [see Warnings and Precautions (5.2, 5.4)] . Perform baseline testing for the presence of anti-AAV9...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The most common adverse reactions that occurred in at least 10% of patients were upper respiratory tract infection, upper gastrointestinal symptoms, pyrexia, and headache. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Gene Therapies at 1-833-828-3947 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another product and may not reflect the rates observed in practice. The safety data described in this section reflects exposure of ITVISMA in two clinical studies, Study 1, a randomized, sham-controlled study which evaluated the safety of ITVISMA in 126 patients with spinal muscular atrophy (SMA) and Study 2, an open-label-single arm study which evaluated safety of ITVISMA in 27 patients with SMA who were previously treated with nusinersen (at least 4 months washout) or risdiplam (at least 15 days washout). In Study 1, a total of 75 patients received a single intrathecal injection of ITVISMA at a fixed dose of 1.2 x 10 14 vg and 51 patients underwent a sham-procedure [see Clinical Studies (14)] . In Study 2, a total of 27 patients received a single intrathecal injection of ITVISMA at a fixed dose of 1.2 x 10 14 vg. The patients were followed for a duration of 52 weeks for both studies. In Study 1, serious adverse reactions were reported in four patients (5%) including elevated liver enzymes (n=1), sensory disturbance (n=2), and vomiting (n=1). The most frequent adverse reactions occurring in ≥ 2% of patients in Study 1 are summarized in Table 3 below. Table 3: Adverse Reactions Occurring in ≥2% of Patients or with higher frequency in ITVISMA-treated Patients compared to Sham group in Study 1 Adverse reactions ITVISMA Sham (N = 75), n (%) (N = 51), n (%) * Is a composite that includes multiple related terms a) Two patients had ALT elevations of 20 times the upper limit of normal (ULN) b) Signs and symptoms that may be suggestive of dorsal root ganglion (DRG) toxicity occurred within 3 weeks of ITVISMA injection and stabilized but remained unresolved at the end of study period. c) Occurred 154 days after the sham procedure and resolved after 15 days without intervention. Upper respiratory tract infection * 31 (41) 15 (29) Pyrexia 19 (25) 12 (24) Upper gastrointestinal symptoms * 20 (27) 8 (16) Hepatic enzyme increased * 6 (8) a 5 (10) Headache 8 (11) 2 (4) Dizziness 4 (5) 1 (2) Pain in extremity 3 (4) 1 (2) Thrombocytopenia * 3 (4) 0 Sensory disturbance * 2 (3) b 1 (2) c The safety evaluated in Study 2 did not identify any additional safety events with ITVISMA administration. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of ZOLGENSMA, a similar product containing the same active ingredient (onasemnogene abeparvovec) administered intravenously. Because these reactions are reported voluntarily, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders : thrombotic microangiopathy Hepatobiliary Disorders : acute liver failure (fatal and non-fatal), acute liver injury General Disorders and Administration Site Conditions : pyrexia, infusion-related reactions Investigations : troponin increased

Drug Interactions

7 DRUG INTERACTIONS Adjust patient’s vaccination schedule to accommodate concomitant corticosteroid administration prior to and following ITVISMA injection [see Dosage and Administration (2.1)] . Certain vaccines, such as measles, mumps, and rubella (MMR) and varicella, are contraindicated for patients on a substantially immunosuppressive steroid dose (i.e., ≥ 2 weeks of daily receipt of 20 mg or 2 mg/kg body weight of prednisone or equivalent). Adjust patient’s vaccination schedule to accommodate concomitant corticosteroid administration prior to and following ITVISMA injection. ( 7 )

Contraindications

4 CONTRAINDICATIONS None. None. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no clinical studies in pregnant women to inform a product-associated risk. There are no available data in animal embryo-fetal development studies with ITVISMA. It is not known whether ITVISMA has the potential to be transferred to the fetus. Therefore, women who are pregnant or desire to become pregnant should only be treated with ITVISMA after a thorough benefit-risk evaluation. In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied ITVISMA is supplied as a sterile, preservative-free, clear to slightly opaque, colorless to faint white suspension for intrathecal injection. ITVISMA contains 4 × 10 13 vg per mL. Each carton of ITVISMA contains a single-dose vial with an extractable volume of not less than 3 mL, containing 1.2 × 10 14 vg. Carton containing one 1.2 × 10 14 vg/3 mL (4 × 10 13 vg/mL) single-dose vial. Container (vial): NDC Number 71894-200-01 Package (carton): NDC Number 71894-200-02 16.2 Storage and Handling Product is shipped and delivered frozen (≤ -60°C [-76°F]) in a single-dose clear vial. Upon receipt, immediately place the carton in a refrigerator at 2°C to 8°C (36°F to 46°F). ITVISMA is stable for 14 days from receipt when stored at 2°C to 8°C (36°F to 46°F). DO NOT REFREEZE. Must use within 14 days of receipt.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.